BACKGROUND & AIMS: A major challenge in the management of nonalcoholic fatty liver disease (NAFLD) is to identify patients with nonalcoholic steatohepatitis (NASH) and early liver fibrosis. The progression of NAFLD is accompanied by distinctive changes in very low density lipoprotein (VLDL), a lipoprotein particle produced exclusively in the liver. Herein, we sought to determine the characteristics of VLDL profiles associated with NASH and liver fibrosis. METHODS: We evaluated VLDL profiles of 128 patients from a single centre NAFLD registry, and examined VLDL size, total and subclass VLDL concentrations in relation to NAFLD activity score (NAS), steatohepatitis and liver fibrosis as determined by liver biopsy. RESULTS: A near linear relationship was observed between mean VLDL particle size and NAFLD activity score (NAS). In multivariate models, VLDL particle size was significantly associated with both NAS and NASH, after adjustment for BMI and diabetes. A decrease in small VLDL particle concentration was associated with more advanced liver fibrosis. In receiver operative characteristic analyses, mean VLDL size performed similarly to cytokeratin 18 in predicting NASH, whereas small VLDL particle concentration had similar performance to NAFLD fibrosis score in predicting stage 2 or above liver fibrosis. CONCLUSIONS: The increase in mean VLDL size in NASH and decrease in small VLDL particle concentration in liver fibrosis likely reflect changes in the number and state of hepatocytes associated with NASH and fibrosis. In addition to its value in risk stratification of cardiovascular diseases, circulating VLDL profile may provide information for the staging of NAFLD disease severity.
BACKGROUND & AIMS: A major challenge in the management of nonalcoholic fatty liver disease (NAFLD) is to identify patients with nonalcoholic steatohepatitis (NASH) and early liver fibrosis. The progression of NAFLD is accompanied by distinctive changes in very low density lipoprotein (VLDL), a lipoprotein particle produced exclusively in the liver. Herein, we sought to determine the characteristics of VLDL profiles associated with NASH and liver fibrosis. METHODS: We evaluated VLDL profiles of 128 patients from a single centre NAFLD registry, and examined VLDL size, total and subclass VLDL concentrations in relation to NAFLD activity score (NAS), steatohepatitis and liver fibrosis as determined by liver biopsy. RESULTS: A near linear relationship was observed between mean VLDL particle size and NAFLD activity score (NAS). In multivariate models, VLDL particle size was significantly associated with both NAS and NASH, after adjustment for BMI and diabetes. A decrease in small VLDL particle concentration was associated with more advanced liver fibrosis. In receiver operative characteristic analyses, mean VLDL size performed similarly to cytokeratin 18 in predicting NASH, whereas small VLDL particle concentration had similar performance to NAFLD fibrosis score in predicting stage 2 or above liver fibrosis. CONCLUSIONS: The increase in mean VLDL size in NASH and decrease in small VLDL particle concentration in liver fibrosis likely reflect changes in the number and state of hepatocytes associated with NASH and fibrosis. In addition to its value in risk stratification of cardiovascular diseases, circulating VLDL profile may provide information for the staging of NAFLD disease severity.
Authors: Andrew Paul DeFilippis; Michael J Blaha; Seth S Martin; Robert M Reed; Steven R Jones; Khurram Nasir; Roger S Blumenthal; Matthew J Budoff Journal: Atherosclerosis Date: 2013-01-29 Impact factor: 5.162
Authors: Dick C Chan; Gerald F Watts; SengKhee Gan; Annette T Y Wong; Esther M M Ooi; P Hugh R Barrett Journal: Arterioscler Thromb Vasc Biol Date: 2010-02-11 Impact factor: 8.311
Authors: Z G Jiang; Y Tsugawa; E B Tapper; M Lai; N Afdhal; S C Robson; K J Mukamal Journal: Aliment Pharmacol Ther Date: 2015-04-27 Impact factor: 8.171
Authors: Ariel E Feldstein; Anna Wieckowska; A Rocio Lopez; Yao-Chang Liu; Nizar N Zein; Arthur J McCullough Journal: Hepatology Date: 2009-10 Impact factor: 17.425
Authors: Rachel H Mackey; Samia Mora; Alain G Bertoni; Christina L Wassel; Mercedes R Carnethon; Christopher T Sibley; David C Goff Journal: Diabetes Care Date: 2015-01-15 Impact factor: 19.112
Authors: Z Gordon Jiang; Bynvant Sandhu; Linda Feldbrügge; Eric U Yee; Eva Csizmadia; Shuji Mitsuhashi; Jinhe Huang; Nezam H Afdhal; Simon C Robson; Michelle Lai Journal: Clin Gastroenterol Hepatol Date: 2017-11-21 Impact factor: 11.382
Authors: Kathleen E Corey; Laura A Wilson; Akif Altinbas; Katherine P Yates; David E Kleiner; Raymond T Chung; Ronald M Krauss; Naga Chalasani Journal: Aliment Pharmacol Ther Date: 2019-03-10 Impact factor: 8.171
Authors: Zhenghui G Jiang; Elliot B Tapper; Misung Kim; Margery A Connelly; Sarah A Krawczyk; Eric U Yee; Mark A Herman; Kenneth J Mukamal; Michelle Lai Journal: J Clin Gastroenterol Date: 2018 May/Jun Impact factor: 3.062
Authors: R Livadariu; D Timofte; A Trifan; R Danila; L Ionescu; A M Sîngeap; D Ciobanu Journal: Acta Endocrinol (Buchar) Date: 2018 Jan-Mar Impact factor: 0.877
Authors: Jari E Kaikkonen; Peter Würtz; Emmi Suomela; Miia Lehtovirta; Antti J Kangas; Antti Jula; Vera Mikkilä; Jorma S A Viikari; Markus Juonala; Tapani Rönnemaa; Nina Hutri-Kähönen; Mika Kähönen; Terho Lehtimäki; Pasi Soininen; Mika Ala-Korpela; Olli T Raitakari Journal: Hepatology Date: 2016-12-24 Impact factor: 17.425